This Core provides a complete set of services to the University of Michigan Nathan Shock Center (UM-NSC) scientists. These services include the production of transgenic mice, transgenic rats, and gene targeted ("knockout") mice from embryonic stem (ES) cells. Transgenic mice are used in many ways, including the tissue specific gene overexpression, production of animal models of human disease, and correction of disease phenotypes. ES cell technology is used to establish animal models of recessive genetic disease and to characterize functional effects of gene loss and subtle changes in genes. Other available services are rederivation of pathogen free mice and rats, and mouse embryo cryopreservation and recovery. The Core maintains specialized reagents for transgenic and gene targeting research. The availability of this Core obviates the need for Center members to invest in expensive equipment and specialized training in transgenic technology. Consultation on all aspects of transgenic and gene targeting research is provided, from the design of DNA constructs to gene expression analysis. Guaranteed Production of Transgenic Mice and Rats: We deliver an average of nine transgenic founder mice and nine founder rats per transgenic order. We guarantee that at least three founders will be produced for each DNA construct submitted to the Core. Production of Gene Targeted ES Cells: The Core will electroporate pluripotent mouse ES cells with gene targeting vectors, pick 480 ES cell clones, and provide DNA from the clones for genetic screening. The Core will expand gene targeted ES cell clones and prepare them for the blastocyst microinjection. Blastocyst Microinjection: The Core guarantees that at least 50 blastocysts will be microinjected to produce ES-cell mouse chimeras. Investigators will breed the chimeras for germline transmission. Commensurate with Center Member usage in the last five years, we project annual demand of 20 orders for transgenic mouse production, one order for transgenic rats, 6 orders for production of gene targeted ES cells, and 15 orders for blastocyst microinjections to make chimeras. In exchange for Center support, UM-NSC scientists will receive a 40% discount on the recharge rate for these services.